Abstract
Peptide mimicry employing a combination of aza-amino acyl proline and indolizidinone residues has been used to develop allosteric modulators of the prostaglandin F2α receptor. The systematic study of the N-terminal phenylacetyl moiety and the conformation and side chain functions of the central turn dipeptide residue has demonstrated the sensitive relationships between modulator activity and topology. Examination of aza-Gly-Pro and aza-Phe-Pro analogs 2a and 2b in a murine preterm labor model featuring treatment with lipopolysaccharide demonstrated their capacity to extend significantly (>20 h) the average time of delivery offering new prototypes for delaying premature birth.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Animals
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Aza Compounds / therapeutic use*
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Escherichia coli / chemistry
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Female
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Indolizidines / chemistry*
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Lipopolysaccharides
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Mice
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Molecular Mimicry
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Peptides / chemical synthesis
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Peptides / chemistry
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Peptides / therapeutic use*
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Pregnancy
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Premature Birth / chemically induced
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Premature Birth / prevention & control*
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Proline / analogs & derivatives*
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Receptors, Prostaglandin / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
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Tocolytic Agents / chemical synthesis
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Tocolytic Agents / chemistry
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Tocolytic Agents / therapeutic use*
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Uterine Contraction / drug effects
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Uterus / drug effects
Substances
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Aza Compounds
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Indolizidines
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Lipopolysaccharides
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Peptides
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Receptors, Prostaglandin
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Tocolytic Agents
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prostaglandin F2alpha receptor
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Proline